Copper chemoselectivity

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

The complexes [Cu(NHC)(MeCN)][BF ], NHC = IPr, SIPr, IMes, catalyse the diboration of styrene with (Bcat) in high conversions (5 mol%, THF, rt or reflux). The (BcaO /styrene ratio has also an important effect on chemoselectivity (mono-versus di-substituted borylated species). Use of equimolecular ratios or excess of BCcat) results in the diborylated product, while higher alkene B(cat)j ratios lead selectively to mono-borylated species. Alkynes (phenylacetylene, diphenylacety-lene) are converted selectively (90-95%) to the c/x-di-borylated products under the same conditions. The mechanism of the reaction possibly involves a-bond metathetical reactions, but no oxidative addition at the copper. This mechanistic model was supported by DFT calculations [68]. 

Tandem azidination- and hydroazidination-Hiiisgen [3 +2] cycloadditions of ynamides are regioselective and chemoselective, leading to the synthesis of chiral amide-substituted 1,2,3-triazoles <06OBC2679>. A series of diversely l-substituted-4-amino-l,2,3-triazoles 132 were synthesized by the copper-catalyzed [3+2] cycloaddition between azides 130 and ynamides 131 <06T3837>. 

There are several guidelines that should be followed in order to increase the chemoselectivity of the monoadduct. Firstly, radical concentration must be low in order to suppress radical termination reactions (rate constant of activation [fcal and fca2] < < rate constant of deactivation kd t andfcd2]). Secondly, further activation of the monoadduct should be avoided ( al> >kd2). Lastly, formation of oligomers should be suppressed, indicating that the rate of deactivation (kd 2[Cu"LmX]) should be much larger than the rate of propagation ( [alkene]). Alkyl halides for copper-catalyzed ATRA are typically chosen such that if addition occurs, then the newly... 

Glycosyl esters with remote functionality constitute a relatively new class of O-carbonyl glycosyl donors, which fulfill the prospect of mild and chemoselective activation protocols (Scheme 3.22). For example, Kobayashi and coworkers have developed a 2-pyridine carboxylate glycosyl donor 134 (Y = 2-pyridyl), which is activated by the coordination of metal Lewis acid (El+) to the Lewis basic pyridine nitrogen atom and ester carbonyl oxygen atom [324]. In the event, 2-pyridyl (carbonyl) donor 134 and the monosaccharide acceptor were treated with copper(II) triflate (2.2 equiv) in diethyl ether at —50 °C, providing the disaccharide 136 in 70% (a P,... 

In 2003, Velusamy and Punniyamurthy reported on a copper(II)-catalyzed C—H oxidation of alkylbenzenes and cyclohexane to the corresponding ketones with 30% hydrogen peroxide (Scheme 131). The reaction was catalyzed by the copper complex 192a depicted in Scheme 131 and yields were high in the case of alkylbenzenes (82-89%) whereas cyclohexanone was obtained with a low yield of 18%. Chemoselectivity was very high in every case neither aromatic oxidation nor oxidation at another position of the alkyl chain was observed. 

Examples are known where intermolecular carbenoid transformations between diazomalonates or certain diazoketones and appropriate olefins result in competition between formation of cyclopropane and products derived from allylic C—H insertion2-4. For example, catalytic decomposition of ethyl diazopyruvate in the presence of cyclohexene gave the 7-ejco-substituted norcarane 93 together with a small amount of the allylic C—H insertion product 94 (equation 95)142 143. In some cases, e.g. rhodium(II) decomposition of a-diazo-j8-ketoester 95, the major pathway afforded C—H insertion products 96 and 97 with only a small amount of the cyclopropane derivative 98. In contrast, however, when a copper catalyst was employed for this carbenoid transformation, cyclopropane 98 was the dominant product (equation 96)144. The choice of the rhodium(II) catalyst s ligand can also markedly influence the chemoselectivity between cyclopropanation and C—H... 

Carbenoid transformations involving competition between intramolecular cyclopropa-nation and /8-hydride elimination have been investigated149. The chemoselectivity of these catalytic transformations can be effectively controlled by the choice of catalyst. Rhodium(II) trifluoroacetate catalysed decomposition of diazoketone 111 proceeds cleanly to give only enone 112. However, rhodium(II) acetate or bis-(iV-t-butylsalicyladiminato) copper(II) cu(TBs)2 provides exclusively cyclopropanation product 113 (equation 102)149. 

The combinations of chlorotrimethylsilane-hexamethylphosphoramide (HMPA) or chlorotrimethylsi-lane-4-(dimethylamino)pyridine (DMAP) are also powerful accelerants for copper(I)-catalyzed Grignard conjugate additions,33 and stoichiometric organocopper and homocuprate additions (Scheme 21 ).36 However, these reactions must be performed in tetrahydrofuran instead of ether.37 These procedures are noted for their high yields with stoichiometric quantities of Grignard reagents, excellent chemoselectivity and efficiency with a,3-unsaturated amides and esters and enals.58 Typically, additions to enals proceed via the S-trans conformers to afford stereo-defined silyl enol ethers for example, enals (122) and (124) give the ( )-silyl enol ether (123) and (Z)-silyl enol ether (125), respectively. 

A simple example that also shows some chemoselectivity is the preparation of the ketones 12 R = Et or Pr by reaction of the bromoacid chloride 11 with the appropriate dialkyl copper lithium. The bromoacid 10 is available and can be converted into a range of bromoketones by this method.3... 

Mannam S, Alamsetti SK, Sekar G (2007) Aerobic, chemoselective oxidation of alcohols to carbonyl compounds catalyzed by a DABCO-copper complex under mild conditions. Adv Synth Catal 349(14-15) 2253-2258... 

The Ullmann coupling, being a copper-catalyzed N-arylation, is known to be more sluggish than the corresponding palladium-catalyzed transformation. Even so, Wu and coworkers succeeded to accelerate reaction times down to only one hour with preserved chemoselectivity (Scheme 26) [93]. A set of aromatic azaheterocycles produced yields of 49-91% after 1 -22 hours of microwave heating. 

The intermolecular C-H insertion of alkanes is very chemoselective, as is illustrated by the reaction with 2-methylbutane [4]. The only C-H transformation observed occurs at the methine site to form 21 in 68 % ee. This result is very different from the rhodium carboxylate-catalyzed reactions of ethyl diazoacetate with 2-methylbutane, which gives rise to all four C-H insertion products [16], Improved regioselectivity has recently been achieved in the intermolecular C-H insertion chemistry of ethyl diazoacetate by using either copper [17] or silver [18] scorpionate catalysts, but enantioselective versions of these reactions are not known. 

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